Abstract
In patients with reperfusion after ischemia and early development of diabetes, neutrophils can attach to blood vessel walls and release their aggressive bactericide agents, which damage the vascular walls. Insulin and 17β-estradiol (E2) relieve the vascular complications observed in metabolic disorders. In contrast, glucagon plays an essential role in the pathophysiology of diabetes. We studied the effect of hormones on neutrophil secretion during adhesion to fibronectin. Amino acid analysis revealed that proteins secreted by neutrophils are characterized by a stable amino acid profile enriched with glutamate, leucine, lysine, and arginine. The total amount of secreted proteins defined as the sum of detected amino acids was increased in the presence of insulin and reduced in the presence of glucagon. E2 did not affect the amount of protein secretion. Proteome analysis showed that in the presence of insulin and E2, neutrophils secreted metalloproteinases MMP-9 and MMP-8 playing a key role in modulation of the extracellular matrix. In contrast, glucagon induced the secretion of cathepsin G, a key bactericide protease of neutrophils. Cathepsin G can promote the development of vascular complications because of its proinflammatory activity and ability to stimulate neutrophil adhesion via the proteolysis of surface receptors.
Highlights
Neutrophils, or polymorphonuclear leukocytes, play an important role in host defense against bacterial or fungal pathogens due to their ability to penetrate into infected tissue and phagocytose and kill microbes
We studied the secretion of neutrophils in the process of adhesion to substrates coated with fibronectin, the extracellular matrix protein, since neutrophils exhibit only a priming activation when adhered to fibronectin
Neutrophils that adhered to fibronectin in the presence of insulin secreted the same proteins as the control cells and, in addition, MMP-9 and matrix metalloproteinase 8 (MMP-8) (Figure 3(b); Table 2)
Summary
Neutrophils, or polymorphonuclear leukocytes, play an important role in host defense against bacterial or fungal pathogens due to their ability to penetrate into infected tissue and phagocytose and kill microbes. Inhibition of glucagon secretion and stimulation of insulin release contribute to a decrease in glucose with respect to the action of GLP-1 [17]. GLP-1 receptor agonists, DPP-4 inhibitors, and metformin have beneficial effects on cardiovascular complications in patients with type 2 diabetes, as well as in patients with reperfusion after ischemia [20,21,22]. In addition to this “genomic” signalling pathway, a “rapid, nonnuclear” signalling pathway mediated by cell membrane-associated estrogen receptors has been recognized This nonnuclear signalling appears to be critical for the protective effects of estrogen in the cardiovascular system [28,29,30]. We used scanning electron microscopy to study the morphology of the attached neutrophils, as well as amino acid analysis and mass spectrometry to study the amount and composition of secreted proteins
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